Analysis of the crystal structure of E. coli RNase H indicates a protein of a five-stranded beta-sheet surrounded by five alpha-helices. Conserved, essential carboxylic acid amino acids probably bind Mg++ and thereby initiate an interaction between the enzyme and the substrate. These negatively charged, conserved amino acids converge with other conserved residues on one face of the molecule. Retroviral and yeast RNase HI have additional domains which may affect the location and/or function of their RNases H. The RNase H domain of yeast functions without the remainder of the protein whereas the retroviral RNase H exhibits a requirement for most of the polymerase domain for maximal activity.